Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer

Transfer RNA (tRNA) activity is tightly regulated to provide a physiological protein translation, and tRNA chemical modifications control its function in a complex with ribosomes and messenger RNA5 (mRNA5). In this regard, the correct hypermodification of position G37 of phenylalanine-tRNA, adjacent...

Descripción completa

Detalles Bibliográficos
Autores: Rosselló Tortella, Margalida, Llinàs Arias, Pere, Sakaguchi, Yuriko, Miyauchi, Kenjyo, Davalos, Veronica, Setién, Fernando, Calleja Cervantes, Maria E., Pineyro, David, Martínez Gomez, Jesús, Guil, Sonia, Joshi, Ricky, Villanueva Garatachea, Alberto, Suzuki, Tsutomu, Esteller, Manel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/173469
Acceso en línea:https://hdl.handle.net/2445/173469
Access Level:acceso abierto
Palabra clave:Càncer colorectal
Epigenètica
Colorectal cancer
Epigenetics
id ES_a8f0d760cccc1832406fe24578497dc6
oai_identifier_str oai:recercat.cat:2445/173469
network_acronym_str ES
network_name_str España
repository_id_str
spelling Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancerRosselló Tortella, MargalidaLlinàs Arias, PereSakaguchi, YurikoMiyauchi, KenjyoDavalos, VeronicaSetién, FernandoCalleja Cervantes, Maria E.Pineyro, DavidMartínez Gomez, JesúsGuil, SoniaJoshi, RickyVillanueva Garatachea, AlbertoSuzuki, TsutomuEsteller, ManelCàncer colorectalEpigenèticaColorectal cancerEpigeneticsTransfer RNA (tRNA) activity is tightly regulated to provide a physiological protein translation, and tRNA chemical modifications control its function in a complex with ribosomes and messenger RNA5 (mRNA5). In this regard, the correct hypermodification of position G37 of phenylalanine-tRNA, adjacent to the anticodon, is critical to prevent ribosome frameshifting events. Here we report that the tRNA-yW Synthesizing Protein 2 (TYW2) undergoes promoter hypermethylation-associated transcriptional silencing in human cancer, particularly in colorectal tumors. The epigenetic loss of TYW2 induces guanosine hypomodification in phenylalanine-tRNA, an increase in -1 ribosome frameshift events, and down-regulation of transcripts by mRNA decay, such as of the key cancer gene ROBO1. Importantly, TYW2 epigenetic inactivation is linked to poor overall survival in patients with early-stage colorectal cancer, a finding that could be related to the observed acquisition of enhanced migration properties and epithelial-to-mesenchymal features in the colon cancer cells that harbor TYW2 DNA methylation-associated loss. These findings provide an illustrative example of how epigenetic changes can modify the epitranscriptome and further support a role for tRNA modifications in cancer biology.National Academy of Sciences2021202120202021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion9 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/173469Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1073/pnas.2003358117Proceedings of The National Academy of Sciences of The United States of America, 2020, vol. 117, num. 34, p. 20785-20793https://doi.org/10.1073/pnas.2003358117cc by (c) Rosselló Tortella et al., 2020http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1734692026-05-29T05:05:01Z
dc.title.none.fl_str_mv Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer
title Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer
spellingShingle Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer
Rosselló Tortella, Margalida
Càncer colorectal
Epigenètica
Colorectal cancer
Epigenetics
title_short Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer
title_full Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer
title_fullStr Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer
title_full_unstemmed Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer
title_sort Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer
dc.creator.none.fl_str_mv Rosselló Tortella, Margalida
Llinàs Arias, Pere
Sakaguchi, Yuriko
Miyauchi, Kenjyo
Davalos, Veronica
Setién, Fernando
Calleja Cervantes, Maria E.
Pineyro, David
Martínez Gomez, Jesús
Guil, Sonia
Joshi, Ricky
Villanueva Garatachea, Alberto
Suzuki, Tsutomu
Esteller, Manel
author Rosselló Tortella, Margalida
author_facet Rosselló Tortella, Margalida
Llinàs Arias, Pere
Sakaguchi, Yuriko
Miyauchi, Kenjyo
Davalos, Veronica
Setién, Fernando
Calleja Cervantes, Maria E.
Pineyro, David
Martínez Gomez, Jesús
Guil, Sonia
Joshi, Ricky
Villanueva Garatachea, Alberto
Suzuki, Tsutomu
Esteller, Manel
author_role author
author2 Llinàs Arias, Pere
Sakaguchi, Yuriko
Miyauchi, Kenjyo
Davalos, Veronica
Setién, Fernando
Calleja Cervantes, Maria E.
Pineyro, David
Martínez Gomez, Jesús
Guil, Sonia
Joshi, Ricky
Villanueva Garatachea, Alberto
Suzuki, Tsutomu
Esteller, Manel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer colorectal
Epigenètica
Colorectal cancer
Epigenetics
topic Càncer colorectal
Epigenètica
Colorectal cancer
Epigenetics
description Transfer RNA (tRNA) activity is tightly regulated to provide a physiological protein translation, and tRNA chemical modifications control its function in a complex with ribosomes and messenger RNA5 (mRNA5). In this regard, the correct hypermodification of position G37 of phenylalanine-tRNA, adjacent to the anticodon, is critical to prevent ribosome frameshifting events. Here we report that the tRNA-yW Synthesizing Protein 2 (TYW2) undergoes promoter hypermethylation-associated transcriptional silencing in human cancer, particularly in colorectal tumors. The epigenetic loss of TYW2 induces guanosine hypomodification in phenylalanine-tRNA, an increase in -1 ribosome frameshift events, and down-regulation of transcripts by mRNA decay, such as of the key cancer gene ROBO1. Importantly, TYW2 epigenetic inactivation is linked to poor overall survival in patients with early-stage colorectal cancer, a finding that could be related to the observed acquisition of enhanced migration properties and epithelial-to-mesenchymal features in the colon cancer cells that harbor TYW2 DNA methylation-associated loss. These findings provide an illustrative example of how epigenetic changes can modify the epitranscriptome and further support a role for tRNA modifications in cancer biology.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/173469
url https://hdl.handle.net/2445/173469
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1073/pnas.2003358117
Proceedings of The National Academy of Sciences of The United States of America, 2020, vol. 117, num. 34, p. 20785-20793
https://doi.org/10.1073/pnas.2003358117
dc.rights.none.fl_str_mv cc by (c) Rosselló Tortella et al., 2020
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Rosselló Tortella et al., 2020
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 9 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869415959474733056
score 15,812429

Similares en LA Referencia